Tailoring a Low Young Modulus for a Beta Titanium Alloy by Combining Severe Plastic Deformation with Solution Treatment

The present paper analyzed the microstructural characteristics and the mechanical properties of a Ti–Nb–Zr–Fe–O alloy of β-Ti type obtained by combining severe plastic deformation (SPD), for which the total reduction was of ε_tot = 90%, with two variants of super-transus solution treatment (ST). The objective was to obtain a low Young’s modulus with sufficient high strength in purpose to use the alloy as a biomaterial for orthopedic implants. The microstructure analysis was conducted through X-ray diffraction (XRD), scanning electron microscopy (SEM), and high-resolution transmission electron microscopy (HRTEM) investigations. The analyzed mechanical properties reveal promising values for yield strength (YS) and ultimate tensile strength (UTS) of about 770 and 1100 MPa, respectively, with a low value of Young’s modulus of about 48–49 GPa. The conclusion is that satisfactory mechanical properties for this type of alloy can be obtained if considering a proper combination of SPD + ST parameters and a suitable content of β-stabilizing alloying elements, especially the Zr/Nb ratio.     

Vanishing nematic order beyond the pseudogap phase in overdoped cuprate superconductors

During the last decade, translational and rotational symmetry-breaking phases—density wave order and electronic nematicity—have been established as generic and distinct features of many correlated electron systems, including pnictide and cuprate superconductors. However, in cuprates, the relationship between these electronic symmetry-breaking phases and the enigmatic pseudogap phase remains unclear. Here, we employ resonant X-ray scattering in a cuprate high-temperature superconductor La1.6−xNd0.4SrxCuO4 (Nd-LSCO) to navigate the cuprate phase diagram, probing the relationship between electronic nematicity of the Cu 3d orbitals, charge order, and the pseudogap phase as a function of doping. We find evidence for a considerable decrease in electronic nematicity beyond the pseudogap phase, either by raising the temperature through the pseudogap onset temperature T* or increasing doping through the pseudogap critical point, p*. These results establish a clear link between electronic nematicity, the pseudogap, and its associated quantum criticality in overdoped cuprates. Our findings anticipate that electronic nematicity may play a larger role in understanding the cuprate phase diagram than previously recognized, possibly having a crucial role in the phenomenology of the pseudogap phase.

There is a growing realization that the essential physics of the cuprate high-temperature superconductors, and perhaps other strongly correlated materials, involves a rich interplay between different electronic symmetry-breaking phases (1–3) like superconductivity, spin or charge density wave (SDW or CDW) order (4–7), antiferromagnetism, electronic nematicity (8–14), and possibly other orders such as pair density wave order (15) or orbital current order (16).One or more of these orders may also be linked with the existence of a zero-temperature quantum critical point (QCP) in the superconducting state of the cuprates, similar to heavy-fermion, organic, pnictide, and iron-based superconductors (17–19). The significance of the QCP in describing the properties of the cuprates, as a generic organizing principle where quantum fluctuations in the vicinity of the QCP impact a wide swath of the cuprate phase diagram, remains an open question. Evidence for such a QCP and its influence include a linear in temperature resistivity extending to low temperature, strong mass enhancement via quantum oscillation studies (20), and an enhancement in the specific heat (21) in the field induced normal state, with some of the more-direct evidence for a QCP in the cuprates coming from measurements in the material La1.6−xNd0.4SrxCuO4 (Nd-LSCO). Moreover, the QCP also appears to be the endpoint of the pseudogap phase (21) that is marked, among other features, by transition of the electronic structure from small Fermi surface that is folded or truncated by the antiferromagnetic zone boundary in the pseudogap phase to a large Fermi surface at higher doping (22, 23) that is consistent with band structure calculations (24). However, in the cuprates, neither the QCP nor the change in the electronic structure have been definitively associated with a particular symmetry-breaking phase.In this article, we interrogate the possibility that the cuprates exhibit a connection between electronic nematic order, the pseudogap, and its associated QCP. In the pnictide superconductors, which are similar in many respects to the cuprates, electronic nematic order is more clearly established experimentally, and there have been reports of nematic fluctuations (25), non-Fermi liquid transport (26), and a change in the topology of the Fermi surface associated with a nematic QCP (27). Electronic nematicity refers to a breaking of rotational symmetry of the electronic structure in a manner that is not a straightforward result of crystalline symmetry, such that an additional electronic nematic order parameter beyond the structure would be required to describe the resulting phase. The manifestation of nematic order may therefore depend on the details of the crystal structure of the materials, such as whether the structure is tetragonal or orthorhombic. However, such a state can be difficult to identify in materials that have orthorhombic structures, which would naturally couple to any electronic nematic order and vice versa. Despite these challenges, experimental evidence for electronic nematic order that is distinct from the crystal structure include reports of electronic nematicity from bulk transport (8–10) and magnetometry measurements (11) in YBa2Cu3Oy (YBCO), scanning tunneling microscopy (STM) (13, 14, 28) in Bi2Sr2CaCu2O8+δ (Bi2212), inelastic neutron scattering (12) in YBCO, and resonant X-ray scattering (29) in (La,Nd,Ba,Sr,Eu)₂CuO₄. Moreover, STM studies in Bi2212 have reported intraunit cell nematicity disappearing around the pseudogap endpoint (30), which also seems to be a region of enhanced electronic nematic fluctuations (31, 32). In YBCO, there have also been reports of association between nematicity and the pseudogap onset temperature (9, 11).Here, we use resonant X-ray scattering to measure electronic nematic order in the cuprate Nd-LSCO as a function of doping and temperature to explore the relationship of electronic nematicity with the pseudogap phase. While evidence that a quantum critical point governs a wide swath of the phase diagram in hole-doped cuprates and is generic to many material systems remains unclear, investigation of Nd-LSCO provides the opportunity to probe the evolution of electronic nematicity over a wide range of doping in the same material system where some of the most compelling signatures of quantum criticality and electronic structure evolution have been observed. These include a divergence in the heat capacity (21), a change in the electronic structure from angle-dependent magnetoresistance (ADMR) measurements (24) in the vicinity of the QCP at x = 0.23, and the onset of the pseudogap (23). Our main result is that we observe a vanishing of the electronic nematic order in Nd-LSCO as hole doping is either increased above x = 0.23, which has been identified as the QCP doping for this system (21), or when temperature is increased above the pseudogap onset temperature T* (23). These observations indicate that electronic nematicity in Nd-LSCO is intimately linked to the pseudogap phase.     

The BISAP score,NLR, CRP,or BUN: Which marker best predicts the outcome of acute pancreatitis?

Acute pancreatitis is a common disease, and the mortality rate can be high. Thus, a risk assessment should be performed early to optimize treatment. We compared simple prognostic markers with the bedside index for severity in acute pancreatitis (BISAP) scoring system to identify the best predictors of severity and mortality.This retrospective study stratified disease severity based on the revised Atlanta criteria. The accuracies of the markers for predicting severe AP (SAP) were assessed using receiver operating characteristic curves. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each marker. Multivariate logistic regression analyses were used to identify independent predictors of SAP and mortality.The area under the curve (AUC) for the BISAP score was classified as fair for predicting SAP. The neutrophil-to-lymphocyte ratio at 48 hours (NLR48 h) and the C-reactive protein level at 48 hours (CRP48 h) had the best AUCs and were independently associated with SAP. When both criteria were met, the AUC was 0.89, sensitivity was 68%, and specificity was 92%. CRP48 h and hematocrit at 48 hours were independently associated with mortality.NLR48 h and CRP48 h were independently associated with SAP but not superior to the BISAP score at admission. Assessing NLR48 h and CRP48H together was most suitable for predicting SAP. The CRP level was a good predictive marker for mortality.     

How efficient is acoustic radiation force impulse elastography for the evaluation of liver stiffness?

Background

In chronic liver diseases, a correct estimation of the severity of liver fibrosis is important for recommendations regarding the treatment. Nowadays, evaluation of fibrosis is done by noninvasive methods such as biochemical scores and transient elastography instead of liver biopsy. The lack of sensitivity to detect fibrosis, because of its heterogeneity is a drawback of liver biopsy (LB).

Objectives

To compare transient elastography (TE) and acoustic radiation force impulse (ARFI) for the evaluation of liver stiffness (LS), against percutaneous LB.

Patients and Methods

Our study comprised of 223 subjects; 52 without fibrosis (38 volunteers and 14 patients with F0 on LB), 36 with F1, 40 with F2, 26 with F3 and 69 with liver cirrhosis (46 with LB and 23 with signs of cirrhosis). For each patient we performed in the same session 10 TE and 5 ARFI measurements. The median values were calculated.

Results

A strong linear correlation (Spearman rho = 0.870) was found between TE and fibrosis (P < 0.0001); there was also a weaker correlation between ARFI and fibrosis (Spearman rho = 0.646; P < 0.0001). TE measurements were also correlated with ARFI measurements (Spearman rho = 0.733, P < 0.0001). The best test for predicting significant fibrosis (F ≥ 2) was TE with a cut-off value of 7.1 kPa (AUROC 0.953). For ARFI, the cut-off value was 1.27 m/s-area under ROC curve (AUROC): 0.890, sensitivity (Se) of 88.7%, specificity (Sp) of 67.5%, positive predictive value (PPV) of 64.5%, and negative predictive value (NPV) of 90% (P = 0.0044). For predicting cirrhosis (F = 4), the optimum cut-off values were 14.4 kPa for TE (AUROC: 0.985, Se: 95.6%, Sp: 94.7%, PPV: 89.2%, NPV: 98%) and 1.7 m/s for ARFI (AUROC: 0.931, Se: 93%, Sp: 86.7%, PPV: 73.6%, NPV: 96.9%) (P = 0.0102).

Conclusions

LS evaluation by means of ARFI is not superior to TE for the assessment of liver fibrosis. ARFI is an accurate test for the diagnosis of cirrhosis.     

Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2 diabetic patients

Aims

Our study addressed the influence of early inflammatory stages of diabetic kidney disease: leukocyte adhesion and monocyte activation (as assessed by intercellular leukocyte adhesion molecule-ICAM-1 and monocyte chemoatractant protein-MCP-1) on the degree of albuminuria. Plasma levels of adiponectin, a possible anti-inflammatory counteracting mechanism, were also studied in correlation to the above-mentioned cytokines.

Methods

79 consecutive type 2 diabetic outpatients and 46 controls were included. Routine laboratory analysis, urinary albumin to creatinine ratio (uACR), plasma adiponectin, plasma ICAM-1 and urinary MPC-1 were assessed.

Results

In multiple regression ICAM-1 (p = 0.004) and adiponectin (p = 0.04) were the main determinants of uACR. Plasma adiponectin positively correlated to ICAM-1 (p = 0.03, r = 0.24).In albuminuric patients (uACR ≥30 mg/g) plasma adiponectin was significantly higher compared to normoalbuminuric ones (uACR <30 mg/g). In albuminuric patients the main determinants of uACR were plasma ICAM-1 and adiponectin. In multiple regression ICAM-1 is the only one that retains statistical significance (p = 0.02). Urinary MCP-1 did not correlate to uACR.

Conclusions

In our type 2 diabetic patients, plasma levels of ICAM-1 and adiponectin are predictive for albuminuria. Urinary MCP-1 does not correlated to uACR. Plasma adiponectin positively correlates to adhesion molecule ICAM-1 in our cohort.     

Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: A systematic review

AIM: To identify severe adverse events (SAEs) leading to treatment discontinuation that occur during antiviral therapy in hepatitis C virus (HCV)-infected cirrhotic patients.METHODS: We identified all the articles published prior to December 2011 in the PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases that presented these data in cirrhotic patients. These studies evaluated the rate of SAEs leading to discontinuation of standard care treatment: Pegylated interferon (PegIFN) alpha 2a (135-180 μg/wk) or PegIFN alpha 2b (1 or 1.5 μg/kg per week) and ribavirin (800-1200 mg/d). Patients with genotype 1 + 4 underwent treatment for 48 wk, whereas those with genotypes 2 + 3 were treated for 24 wk.RESULTS: We included 17 papers in this review, comprising of 1133 patients. Treatment was discontinued due to SAEs in 14.5% of the patients. The most common SAEs were: severe thrombocytopenia and/or neutropenia (23.2%), psychiatric disorders (15.5%), decompensation of liver cirrhosis (12.1%) and severe anemia (11.2%). The proportion of patients who needed to discontinue their therapy due to SAEs was significantly higher in patients with Child-Pugh class B and C vs those with Child-Pugh class A: 22% vs 11.4% (P = 0.003). A similar discontinuation rate was found in cirrhotic patients treated with PegIFN alpha 2a and those treated with PegIFN alpha 2b, in combination with ribavirin: 14.2% vs 13.7% (P = 0.96). The overall sustained virological response rate in cirrhotic patients was 37% (95%CI: 33.5-43.1) but was significantly lower in patients with genotype 1 + 4 than in those with genotype 2 + 3: 20.5% (95%CI: 17.9-24.8) vs 56.5% (95%CI: 51.5-63.2), (P < 0.0001).CONCLUSION: Fourteen point five percent of HCV cirrhotic patients treated with PegIFN and ribavirin needed early discontinuation of therapy due to SAEs, the most common cause being hematological disorders.     

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: A retrospective multicentre study

BackgroundAcoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis.AimTo evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography.MethodsA multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients.ResultsThe best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels > 5× the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively.Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5× the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively.For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5× the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa.ConclusionLiver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels.     

Novel cyano- and amidino-substituted derivatives of styryl-2-benzimidazoles and benzimidazo[1,2-a]quinolines. Synthesis, photochemical synthesis, DNA binding, and antitumor evaluation, part 3

Synthesis of novel cyano- and amidino-substituted styryl-2-benzimidazoles and benzimidazo[1,2-a]quinolines by condensation reactions and photochemical dehydrocyclization and dehydrohalogenation cyclization is described. Thermal denaturation experiments reveal that cyclic derivatives considerably stabilize DNA double helix, while the effect of their acyclic analogues is negligible. According to the spectroscopic study of the interaction of cyclic derivative 19, we propose intercalation of benzimidazo[1,2-a]quinoline moiety into ct-DNA as a dominant interaction underlying biologically relevant effects of this compound, whereas for its acyclic derivative 11, we propose binding into the minor groove of DNA. All compounds show noticeable antiproliferative effect. Morpholino- and chloro-substituted compound 9 is the most active among all acyclic derivatives. All cyclic compounds were 2- to 10-fold more potent, which is correlated with their property to intercalate into DNA. The most active imidazolyl-substituted compound 19 inhibits topoisomerase II and induces strong G2/M cell cycle arrest, pointing to the impairment in mitotic progression. Its pronounced selectivity toward colon carcinoma cells encourages further development of this compound as a lead.